Differential responses of human mononuclear phagocytes to mycobacterial lipoarabinomannans: Role of CD14 and the mannose receptor
Differential responses of human mononuclear phagocytes to mycobacterial lipoarabinomannans: Role of CD14 and the mannose receptor
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DOI：
10.1128/iai.66.1.28-35.1998
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发表时间：
1998-01-01
影响因子：
3.1
通讯作者：
Fenton, MJ
中科院分区：
文献类型：
--
作者：
Bernardo, J;Billingslea, AM;Fenton, MJ
CD14是革兰氏阴性细菌脂多糖（LPS）和分枝杆菌脂阿拉伯糖甘露聚糖（LAM）的信号受体，缺乏末端甘露糖基单位（AraLAM）。相反，终甘露糖基化LAM （ManLAM）与巨噬细胞甘露糖受体（MMRc）结合，尽管MMRc作为信号受体的能力此前尚未报道。我们比较了AraLAM和ManLAM在两种单核细胞群（新鲜分离的人外周血单核细胞（PBM）和单核细胞源性巨噬细胞（MDM））中诱导不同反应的能力。检测的反应是趋化性和游离胞质钙（[Ca2+](in)）的短暂变化。我们发现AraLAM而不是ManLAM对PBM和MDM都具有趋化作用，这些细胞在体外向AraLAM的迁移被抗CD14单克隆抗体特异性阻断，这表明CD14介导了对AraLAM的趋化反应。随后，我们发现在PBM亚群中，AraLAM诱导了[Ca2+]（in）水平的短暂升高，而不是MDM。这种反应被抗cd14抗体阻断。相反，ManLAM在MDM亚群中诱导[Ca2+]（In）水平的短暂升高，而在PBM中没有。这种反应被抗cd14或抗mmrc抗体阻断。这些数据表明，MMRc可以作为一种信号受体，并且CD14和MMRc的结合需要引起特异性反应，因此，对LAM（趋化性）的一种反应可以仅通过参与CD14而引起，而不同的反应（[Ca2+]（in）水平的变化）取决于细胞的分化状态和CD14和MMRc的同时参与。
CD14 is a signaling receptor for both gram-negative bacterial lipopolysaccharide (LPS) and mycobacterial lipoarabinomannan (LAM) that lacks terminal mannosyl units (AraLAM). In contrast, terminally mannosylated LAM (ManLAM) binds the macrophage mannose receptor (MMRc), although the ability of the MMRc to serve as a signaling receptor has not been previously reported. We compared the abilities of AraLAM and ManLAM to induce distinct responses in two monocytic cell populations, freshly isolated human peripheral blood monocytes (PBM) and monocyte-derived macrophages (MDM). The responses examined were chemotaxis and transient changes in free cytosolic calcium ([Ca2+](in)). We found that AraLAM but not ManLAM was chemotactic for both PBM and MDM, Migration of these cells in vitro to AraLAM mas specifically blocked by an anti-CD14 monoclonal antibody, suggesting that CD14 mediates the chemotactic response to AraLAM. Subsequently, we found that AraLAM induced a transient rise in [Ca2+](in) levels within a subpopulation of PBM but not MDM. This response was blocked by anti-CD14 antibodies, In contrast, ManLAM induced a transient rise in [Ca2+](in) levels within a subpopulation of MDM but not PBM. This response was blocked by either anti-CD14 or anti-MMRc antibodies. These data suggest that the MMRc can serve as a signaling receptor and that coligation of both CD14 and the MMRc is required to elicit a specific response, Thus, one response to LAM (chemotaxis) can be elicited solely by engaging CD14, whereas a different response (changes in [Ca2+](in) levels) depends on both the differentiation state of the cells and concomitant engagement of CD14 and the MMRc.